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Phenytoin


At a Glance

Why Get Tested?

To determine the level of the drug phenytoin in your blood in order to maintain a therapeutic level and to detect potential for toxicity

When to Get Tested?

At regular intervals to monitor; as needed to detect low or toxic concentrations

Sample Required?

A blood sample drawn from a vein in your arm

Test Preparation Needed?

None

The Test Sample

What is being tested?

Phenytoin is a drug that is used to treat some seizure disorders (see Epilepsy), including complex partial seizures (psychomotor seizures) and seizures that occurr during or after neurosurgery. Phenytoin may be used alone or with phenobarbital or other anticonvulsants. This test measures the amount of phenytoin in the blood.

Seizure disorders affect the brain's ability to transmit electrical impulses and to regulate nerve activity. During a seizure, someone may experience changes in consciousness, alterations in sight, smell, and taste, and may experience uncontrolled muscular convulsions in one or more parts of the body. Phenytoin works by reducing the electrical conductance among brain cells, blocking excessive electrochemical activity occurring in the brain during a seizure.

Anyone can experience a seizure at any age. In many cases, the cause of seizures is not known. The frequency and severity varies from person to person and may change over time. People may experience a single seizure and never have another, may have occasional seizures, or may have recurrent seizures. In rare cases, a person may have a seizure that starts and does not stop without prompt medical intervention.

Phenytoin is prescribed to help prevent the recurrence of certain types of seizures. It has been widely used in the United States since its development in 1938. It is still being prescribed but is beginning to be replaced by newer drugs.

The level of phenytoin in the blood must be maintained within a narrow therapeutic range. If levels are too low, the affected person may experience seizures; if they are too high, the person may experience symptoms associated with phenytoin toxicity. These may include loss of balance and falling, involuntary eye movement from side to side (nystagmus), confusion, slurred speech, tremors, and low blood pressure.

Maintaining a therapeutic level of phenytoin in the blood can be a challenge. Enzymes in the liver process phenytoin at rates that differ from person to person and are affected by age (children metabolize it more quickly while the elderly metabolize it more slowly) and by the health of the liver. When the body has reached its capacity to process phenytoin, small increases in the dose can cause large increases in blood concentration, increasing the severity of side effects and causing phenytoin toxicity.

Phenytoin's total effect can be unpredictable. Dosages must be adjusted slowly until a steady concentration in the blood is reached.The actual amount of drug that it takes to reach this steady state will vary from person to person and may change over time. Health practitioners must also watch for side effects and adverse reactions during initial dosage adjustment and over time. In some cases, the severity of side effects may make it necessary to consider another anti-seizure medication.

Most phenytoin is bound to protein in the bloodstream; it is the unbound "free" portion that is active. If a person has a lower than normal amount of protein in their blood, such as low albumin in liver failure, then the person may have an excess of active phenytoin. Phenytoin can also interact with other drugs and increase or decrease the other medications' effectiveness. it is important to always discuss with a health practitioner all medications being taken to determine if drug interactions are a possibility.

How is the sample collected for testing?

A blood sample is obtained by inserting a needle into a vein in the arm.

Is any test preparation needed to ensure the quality of the sample?

No test preparation is needed.

The Test

How is it used?

The phenytoin test is used to measure and monitor the amount of phenytoin in the blood and to determine whether drug concentrations are in the therapeutic range.It may be ordered every few days when a person first begins taking phenytoin to help adjust the dose to the desired blood level.The test is then ordered at regular intervals and as needed to monitor blood concentrations.One or more phenytoin tests may be ordered if a person starts or stops taking additional medications (to judge their effect, if any, on phenytoin levels) and may be ordered if the person has a seizure or if a health practitioner suspects toxicity.

Usually, a total phenytoin test is used to monitor levels. In the blood, phenytoin is highly bound to serum proteins. Only the portion of phenytoin that is unbound or "free" is pharmacologically active. Under normal conditions, the balance between bound and unbound phenytoin in the blood is relatively stable, so measuring the total phenytoin (bound plus unbound) is appropriate for monitoring therapeutic levels. However, in certain conditions and disease states, that balance can be upset, the percentage of free or active phenytoin can increase, and the person may experience symptoms of toxicity even though their total phenytoin result falls within therapeutic range. In such cases, health practitioners may order a free phenytoin test to monitor the person's levels.

When is it ordered?

Phenytoin is ordered frequently when a person begins phenytoin treatment and when/if a person's medications change (other drugs are started, stopped, or changed) or if there is a change in the status of their health. Once stable blood concentrations in the therapeutic range have been achieved, phenytoin is monitored at regular intervals to ensure that it remains in this range.

The test may be ordered when a person's condition does not appear to be responding to phenytoin (e.g, he or she continues to have seizures) to determine whether the concentration is too low, the medication is ineffective, and/or to determine if the person is complying with therapy (taking the phenytoin regularly). The test may also be ordered when a person experiences side effects and/or exhibits symptoms that the health practitioner suspects may be due to toxicity. Toxic symptoms can affect the mouth, cardiovascular and nervous systems, and the eyes and include:

  • Swelling of the gums and/or lymph nodes
  • Hirsutism
  • Insomnia
  • Nausea
  • Confusion and irritability
  • Difficulty swallowing
  • Fatigue
  • Fever
  • Rashes
  • Involuntary eye movement
  • Abnormal heartbeat
  • Low blood pressure

A free phenytoin level may be ordered when a person has a condition in which the percentage of free or active phenytoin may be increased. Some examples of these conditions include:

  • Kidney failure
  • Liver disease
  • Low blood levels of albumin (hypoalbuminemia)
  • If the person is taking other medications such as aspirin, naproxen or ibuprofen

What does the test result mean?

The therapeutic ranges for adults taking phenytoin have been established at 10.0-20.0 mcg/mL for total phenytoin (bound plus unbound) and 1.0-2.0 mcg/mL for free phenytoin (unbound only).The range for percent free phenytoin is 8-14%.

Within these ranges, most people will respond to the drug without symptoms of toxicity.Response and side effects will be individual, however.Some people will experience seizures at the low end of the therapeutic range and some people will experience excessive side effects at the upper end. People should work closely with their health practitioner to find the dosage and concentration that works the best for them.

In general, when phenytoin results are in the therapeutic range, the person is not having recurrent seizures and is not experiencing significant side effects, then the dosage of phenytoin is adequate. People should not increase, decrease, or stop taking their medication without consulting with their health care provider as it can increase their risk of having a seizure and may affect other medications that they are taking.Dosage determinations and adjustments must be evaluated on a case-by-case basis.

Is there anything else I should know?

People who take phenytoin long-term may develop vitamin D deficiency, numbness in their extremities due to nerve damage (peripheral neuropathy), acne, excessive hair on their face or body, a thickening of facial features, or weakness of their bones.Rarely, a person may develop a severe rash and skin condition that requires hospitalization.

Women who use phenytoin during pregnancy are at an increased risk of having babies born with several types of birth defects.Women who want to become pregnant should talk to their health practitioner.

Phenytoin is sometimes prescribed for other conditions such as trigeminal neuralgia, which causes episodes of sharp pain along the jaw, and other causes of nerve pain.This use must also be monitored.

Phenytoin is not effective for every kind of seizure and will not work for every person.

A large variety of prescribed drugs, over-the-counter medications, and supplements can increase, decrease, or interfere with the concentration of phenytoin in the blood and its effects. Drugs whose effects are reduced by phenytoin include corticosteroids such as prednisone, estrogens, warfarin, and some antidepressants. Phenytoin also can reduce the effectiveness of oral contraceptives and other forms of birth control such as Depo-Provera or implants. Drugs that may increase phenytoin blood levels and toxicity include alcohol, diazepam, certain antidepressants, and omeprazole. The oral absorption of phenytoin can be reduced by antacids containing magnesium, calcium carbonate, calcium salts, or enteral feeding products. Many more drugs interact with phenytoin, so tell your health practitioner about any prescription or over-the-counter drugs, supplements, or herbal products you take.



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